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Take heart

By Andy Coghlan

A SOFTWARE heart beating away on a computer screen is helping to speed up the
study and treatment of heart disease.

Physiome Sciences, of New York City, says that its virtual dog heart
simulates precisely the electrical activities of individual cells and how they
are affected by drugs and other chemicals. The simulations could help drugs
companies to weed out potentially harmful or ineffective drugs without using
animals.

This is the first of many virtual organs the company is developing.
Ultimately, it hopes to recreate the innards of an entire human being, apart
from the brain, inside a computer. “We’re the first company to develop
physiological models of organs on computers,” says Bill Scott, the chief
executive of Physiome.

The company was showing videos of its new computer-generated heart last week
at the Biopartnering Europe conference in London. The videos show the
differences between a normal dog heart and one affected by arrhythmia, an
abnormal beating pattern which can trigger heart attacks.

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The virtual heart is created by putting together mathematical equations
describing the electrical workings of individual heart cells. All the equations
come from data on processes such as cascades of calcium, sodium and potassium
ions through the pores of cells.

“When you hook the cells together, what emerges is the behaviour of a whole
heart,” says Donna Rounds, director of business development at Physiome. At
present, says Scott, the virtual heart only shows electrical activity, but
Physiome plans to include mechanical data such as cell size so that the heart
will change shape as well.

The heart is the result of decades of painstaking work by the company’s
co-founders, Denis Noble, professor of physiology at the University of Oxford,
and Raimond Winslow, associate professor of biomedical engineering at Johns
Hopkins University, Baltimore. The two men worked out the equations that
describe electrical activity in different types of heart cells.

Physiome are already using simulations of normal and diseased
hearts to test the effects of existing and potential drugs. Their researchers
simply slot in numerical details of drug activity into the computer. The data
come from standard cell assays which show, for example, the strength with which
a drug binds to its target. However, cell assays only show how a drug behaves at
the cellular level, whereas the computer model shows how the drugs affect the
whole heart. To date, Physiome has recreated hearts of guinea pigs, rats, mice
and dogs. A model of the human heart is under construction.

Drugs company Hoffman-La Roche has already used the virtual heart to
explain unusual physiological effects of Posicor, a new drug to combat high
blood pressure and angina. Patients on high doses of the drug had unusual
electrocardiograms. Physiome’s heart showed that the drug caused subtle but
harmless alterations to beating cycles.